Walnut By-Products and Elderberry Extracts—Sustainable Alternatives for Human and Plant Health

A current alternative for sustainable development through green chemistry is the replacement of synthetic compounds with natural ones through the superior capitalization of natural resources, with numerous applications in different fields. The benefits of walnuts (Juglans regia L.) and elderberries (Sambucus nigra L.) have been known since ancient times, due to the presence of phytochemicals such as flavonoids, polyphenols, carotenoids, alkaloids, nitrogen-containing compounds, tannins, steroids, anthocyanins, etc. These active compounds have multiple biological activities for human health, including benefits that are antibacterial, antioxidant, anti-inflammatory, antidiabetic, hepatoprotective, antihypertensive, neuroprotective, etc. Like other medicinal plants, the walnut and the elderberry possess important phytosanitary properties (antibacterial, antifungal, and insecticidal) and their extracts can also be used as environmentally safe biopesticides, with the result that they constitute a viable and cheap alternative to environmentally harmful synthetic products. During recent years, walnut by-products and elderberries have attracted the attention of researchers, and investigations have focused on the species’ valuable constituents and active properties. Comparing the information from the literature regarding the phytochemical profile and biological activities, it is highlighted that, apart from the predominant specific compounds, the walnut and the elderberry have common bioactive compounds, which come from six classes (phenols and derivatives, flavonoids, hydroxycinnamic acids, tannins, triterpenoids, and phytosteroids), and act on the same microorganisms. From this perspective, the aim of this review is to provide an overview of the bioactive compounds present in the different constitutive parts of walnut by-products and elderberries, which present a specific or common activity related to human health and the protection of agricultural crops in the context of sustainable development.


Introduction
Maintaining the health of the population, as well as the quality of the environment in which we live, requires the correct management of economic relations, social resources, and, even more importantly, everything that can be considered as natural resources.
In this regard, special interest is given to plants that have been and are used in traditional medicine due to the rich content of their different compounds with bioactive properties.In significant proportions, plants are used in the pharmaceutical and nutritional supplement industry as primary sources for the extraction of natural compounds with beneficial effects, especially for preventive but also therapeutic purposes [1][2][3][4].
Among the fundamental needs of modern industry, because of overexploitation and globalization, are sustainability and the so-called "green chemistry", which involves replacing synthetic compounds with natural ones from plants, in order to capitalize and develop the septum, the woody shell, and the green shell (Figure 1).The kernel is the edibl of the fruit, being widely consumed by humans.The other parts of the walnut (the shell, the dry woody shell, the septum, the bark, the branches, and the leaves) are us various purposes [16,20].The green shell is used in traditional Chinese medicine to fight cancer due to tioxidant properties, as well as for the treatment of pain and for inflammation [21 leaves are used to relieve minor inflammatory skin disorders [22].The walnut she results from the processing of walnuts through a successful process of valorization c another source of active compounds [23,24].The ripe nut fruit is used in confectio while the young form of the fruit is mainly used in the production of liquor [25].
The elder, black elder, or elderberry (Sambucus nigra L.) is used as a medicina ornamental plant.In the Middle Ages, among the ancient Germans, the elderberr considered a holy plant, also being used in traditional medicine [12].In popular trad the elderberry, a species of plants in the group of shrubs in the Adoxaceae family (F 2), is considered the number one antiviral medicine [13,14].The hermaphrodite fl are fragrant, while the leaves have an unpleasant odor when rubbed in the hands.flowers are followed by clusters of small black fruits.Elderberries are a powerful s of essential vitamins and minerals [13].

Chemical Composition
The chemical composition varies within very wide limits due to factors related species, the variety, pedoclimatic conditions, the harvest period, the degree of rip and extraction conditions, as well as the analysis and identification methods.The green shell is used in traditional Chinese medicine to fight cancer due to its antioxidant properties, as well as for the treatment of pain and for inflammation [21].The leaves are used to relieve minor inflammatory skin disorders [22].The walnut shell that results from the processing of walnuts through a successful process of valorization can be another source of active compounds [23,24].The ripe nut fruit is used in confectionery, while the young form of the fruit is mainly used in the production of liquor [25].
The elder, black elder, or elderberry (Sambucus nigra L.) is used as a medicinal and ornamental plant.In the Middle Ages, among the ancient Germans, the elderberry was considered a holy plant, also being used in traditional medicine [12].In popular tradition, the elderberry, a species of plants in the group of shrubs in the Adoxaceae family (Figure 2), is considered the number one antiviral medicine [13,14].The hermaphrodite flowers are fragrant, while the leaves have an unpleasant odor when rubbed in the hands.These flowers are followed by clusters of small black fruits.Elderberries are a powerful source of essential vitamins and minerals [13].
Molecules 2024, 29, x FOR PEER REVIEW 3 of 22 the septum, the woody shell, and the green shell (Figure 1).The kernel is the edible part of the fruit, being widely consumed by humans.The other parts of the walnut (the green shell, the dry woody shell, the septum, the bark, the branches, and the leaves) are used for various purposes [16,20].The green shell is used in traditional Chinese medicine to fight cancer due to its antioxidant properties, as well as for the treatment of pain and for inflammation [21].The leaves are used to relieve minor inflammatory skin disorders [22].The walnut shell that results from the processing of walnuts through a successful process of valorization can be another source of active compounds [23,24].The ripe nut fruit is used in confectionery, while the young form of the fruit is mainly used in the production of liquor [25].
The elder, black elder, or elderberry (Sambucus nigra L.) is used as a medicinal and ornamental plant.In the Middle Ages, among the ancient Germans, the elderberry was considered a holy plant, also being used in traditional medicine [12].In popular tradition, the elderberry, a species of plants in the group of shrubs in the Adoxaceae family (Figure 2), is considered the number one antiviral medicine [13,14].The hermaphrodite flowers are fragrant, while the leaves have an unpleasant odor when rubbed in the hands.These flowers are followed by clusters of small black fruits.Elderberries are a powerful source of essential vitamins and minerals [13].

Chemical Composition
The chemical composition varies within very wide limits due to factors related to the species, the variety, pedoclimatic conditions, the harvest period, the degree of ripening, and extraction conditions, as well as the analysis and identification methods.

Chemical Composition
The chemical composition varies within very wide limits due to factors related to the species, the variety, pedoclimatic conditions, the harvest period, the degree of ripening, and extraction conditions, as well as the analysis and identification methods.

Chemical Composition of Walnut
The benefits of the walnut, which have been known since ancient times, are due to the presence of some bioactive compounds such as flavonoids, polyphenols, juglones, tannins, steroids, etc. [15][16][17]26].

• Chemical composition of walnut by-products
The extracts from walnut by-products contain a variety of useful compounds compared to the extracts from the walnut kernel.

Chemical Composition of Walnut Leaves
According to Medic et al. [35], who performed the extraction of 0.25 g of leaf powder with methanol in an extract ratio of 1:30 (w/v) leaves: methanol using ultrasonication for 60 min and analyzed the extracts via HPLC-MS, and other research [36][37][38][39][40][41][42], walnut leaves contain a large amount of compounds from the class of hydroxycinnamic acids (neochlorogenic acid and 3-p-coumaroylquinic acid), flavonoids ((+) catechin, procyanidin dimers, and quercetin derivatives), and naphthoquinones (hydrojuglone derivatives, juglone, and sdihydroxytetralone hexoside) (Table 2).Green walnut shell extracts can be obtained using several extraction methods.For example, the green walnut shell extract can be prepared through maceration by stirring the raw material (1 g) in an aqueous ethanol solution (80% ethanol, v/v; 30 mL) at 25 • C for 60 min [43].Ultrasonic assisted extraction (UAE) and supercritical CO 2 extraction were used to increase the extraction yield.For the UAE, the optimal conditions were a temperature of 60 • C, an extraction time of 30 min, and a mixture of 60% ethanol-water [20].For the supercritical CO 2 extraction, the optimal conditions were established as 68 • C and 20% ethanol [44].The total phenol content was determined with the Folin-Ciocâlteu method, using phenolic acids and juglone with ultra-high performance liquid chromatography (UHPLC) [45].Jahanban-Esfahlan et al. [20] presented a summary of the compounds present in the green walnut shell extract.
Furthermore, the dry walnut shell contains compounds from the class of hydroxybenzoic acid derivatives, sterols, mono-and triglicerides, minerals and (calcium, potassium, and iron).For example, Queirós et al. [46] used 2 g of dry crushed walnut shell for Soxhlet extraction with different solvents (dichloromethane, ethanol, and water) and performed the extract analysis via a UV-coupled high-pressure ion exclusion chromatography (HIPCE-UV).

Chemical Composition of the Walnut Septum
As reported by Genovese et al. [50], after the extraction of the walnut septum through ethanolic maceration (10 g of powdered walnut septum in 50 mL of 96% ethanol for 48 h at room temperature) and analysis via HPLC with an ionization mass spectrometry (HPLC/ESI-MS), and several other studies [51][52][53][54], the walnut septum contains an important amount of compounds from the classes of tannins (ellagic acid) and flavonoids (quercitrin) (Table 4).

• Chemical composition of elderberry leaves
According to several studies [12][13][14]18,[58][59][60][61][62][63], elderberry leaves contain a large amount of phenolic compounds (caffeic acid and chlorogenic acid), flavonoids (quercetin-rutinoside), and anthocyanins (cyanidin-glucoside) (Table 5).For example, Kiprovski et al. [62] studied the changes that occurred during ripening in the leaves and fruits of wild and cultivated Sambucus nigra through sonication and analyzed the extracts using HPLC-DAD-ESI-MS.• Chemical composition of elderberry flowers Vujanović et al. [64], after performing the extraction through different methods (maceration, sonication, and microwave-assisted extraction) using different solvents and analyzing the extracts using the LC-MS/MS technique, found that microwave-assisted extraction provides the highest number of bioactive compounds.According to this study and others [18,58,60,64,65], the elderberry flowers contain a large amount of compounds from the classes of phenols (quinic acid), flavonoids (naringenin, 5-O-caffeoylquinic acid, and rutin), and terpenes (ursolic acid) (Table 6).[18], Mocanu and Amariei [12], Pascariu and Israel-Roming [13], and Has , et al. [14] showed that Sambucus fruits contain a number of phytochemical compounds, such as phenolic acid (chlorogenic acid), flavonoids (quercetin-rutinoside), anthocyanins (cyanidin-glucoside), and triterpenoids (ursolic acid and oleanolic acid) (Table 7).In addition, Kiprovski et al. [62] found that cultivated elderberries had a higher content of phenolics compared to wild edible plants.The walnut is a crop of great economic interest.Walnut trees are among the most important hardwood species in the northern hemisphere from an ecological and economic point of view.They are mainly cultivated for timber and nut production but are also attractive ornamental trees in parks.All the component parts are used in various industrial branches, including the food industry.The tasty part of the fruit (the kernel) is eaten fresh or roasted and alone or mixed with other edible products.Abdulwahid et al. [47] have shown that the walnut shell is a low-cost and abundant raw material, making it an attractive option for producing building materials.This can help to reduce the cost of construction and to make environmentally friendly building materials more accessible.According to Fordos et al. [48], the walnut shell is extensively used in agriculture, industrial fields, medicine, cosmetics, and environmental fields.This by-product can be a sustainable, ecological, and low-cost alternative to expensive toxic chemicals.
The benefits of the walnut, due to the presence of numerous bioactive compounds such as polyphenols, flavonoids, naphthoquinones, tannins, tocopherols, fatty acids, alkaloids, etc., are reflected not only on our health (with antibacterial, antioxidant, and anti-inflammatory benefits) but also on plants (the phytosanitary properties-antifungal and insecticidal).Like other medicinal plants, the walnut can be used due to its phytosanitary properties in the form of biopesticides, constituting a safe and cheap alternative compared to synthetic products that can be unfriendly to the environment.

Antibacterial Activity
Studies have shown that all parts of the J. regia plant have antibacterial properties with beneficial effects on the human body.The green shell extracts of J. regia possess a good antibacterial activity on the species E. coli, B. subtilis, P. aeruginosa, and S. aureus [68].Jaiswal et al. [69] showed that juglone inhibits three key enzymes in H. pylori.Antibacterial properties were enhanced if the dried walnut shell was modified with silver nanoparticles [70].
The antibacterial activity also depends on the method of extraction, the type of solvent, and the mixing ratio [24,43].An ethanolic extract with a concentration of 5 mg/mL showed a high antibacterial potential for S. aureus.A concentration of 10 mg/mL was effective against a Gram-positive species (L.monocytogenes) and a Gram-negative species (E.coli).At a concentration of 5 mg/mL, the inhibition rates of S. aureus, B. subtilis, and E. coli bacteria were 85.31-90.26%.Aqueous extracts inhibited Gram-positive bacteria (P.aeruginosa) at a concentration of 100 mg/mL and S. aureus at a concentration of 0.1 mg/mL [71].The walnut shell and leaf extracts also had an antibacterial effect against S. mutans dental caries [72].Gomes et al. [73] studied the antibacterial activity of J. regia, individually and combined with Eucalyptus globulus hydromethanolic extract, and highlighted that the combination of both extracts was most effective against S. aureus from cow's milk.An increase in the antimicrobial effect on E. coli, P. aeruginosa and A. baumannii was observed when using a walnut leaf extract mixed with ZnO nanoparticles [74].Other studies presented the influences of the concentration of the same type of extract and the nature of the solvent used for extraction on the antibacterial activity on Gram-positive bacteria such as E. faecalis and L. monocytogenes [37]; S. epidermidis; B. subtilis; S. aureus [75]; B. cereus [38]; S. epidermidis [39]; and S. arizonae [76].Dolatabadi et al. [77] determined that the aqueous extract had a better inhibition on P. aeruginosa.Huo et al. [78] showed that the walnut root extract had a strong antibacterial effect against P. aeruginosa, S. aureus, E. coli, and P. mirabilis.Extracts from the kernel and peel were proven to have an inhibitory effect on the strains of E. faecium, E. coli, K. pneumoniae, P. aeruginosa [79], and coagulase-negative staphylococci (MIC 3.60-461.75µg/mL) [80].Kavuncuoglu et al. [81] explained that the mathematical model based on Artificial Neural Networks (ANN) can be used to determine the inhibition zone diameter of the walnut extract for twelve bacterial species.Duda-Seiman et al. [82] showed that the alcoholic extract of the walnut kernel had a strong antimicrobial effect on the bacteria S. pyogenes, S. aureus, and P. mirabilis and was completely ineffective at the concentration tested against the Gram-negative bacterium P. aeruginosa.On the other hand, the study of Perreira et al. explained that aqueous extracts at low concentrations (0.1-1 mg/mL) inhibit Gram-positive bacteria (B.cereus, B. subtilis, S. aureus), and at higher concentrations (10-100 mg/mL) they inhibit the Gram-negative ones (P.aeruginosa, E. coli, and K. pneumoniae) [83].Alcoholic septum extracts, according to the study of Genovese et al. [50], exhibited a stronger antibacterial effect on Gram-positive bacteria (S. aureus, S. epidermidis, E. faecalis, and E. faecium) than on Gram-negative strains (E.coli, K. pneumoniae, P. aeruginosa, and P. mirabilis), a fact indicated by lower MIC values.Ethyl acetate extracts from the walnut bark presented a high degree of antimicrobial activity for S. mutans and S. salivarius [84]; the alcoholic extract seemed to be more effective for S. aureus bacteria and less for S. typhi (bacterium Gram-negative) [85]; the aqueous extract, compared to the acetonic one, had a stronger inhibitory effect on the growth of the oral microbial flora [86,87]; and the chloroformic extract showed in vitro antimicrobial activity against dental caries microorganisms (S. mutans, S. sobrinus, A. viscosus) [41], as well as for S. aureus, E. coli, and P. aeruginosa [88].The alcoholic, acetonic, and benzene extracts with the minimum inhibitory concentration of 50 µg/mL to 300 µg/mL inhibited Gram-positive bacteria (B.subtilis and S. aureus) [89].It was also shown that chloroformic and aqueous walnut extracts had microbicidal activity against air microorganisms and the leaf extract was very effective in treating skin acne against the Propioni bacteria [16].

Antifungal Activity
Pathogenic fungi are responsible for crop damage.Attempts are being made to replace fungicidal treatments that use synthetic, polluting chemical substances with more environmentally friendly plant extracts.Studies were carried out on extracts of the woody and green shells of walnuts, and their antifungal activity on cultivated plants, vegetables, and fruits was observed [90][91][92].
In the case of walnut bark extracts, Upadhyay et al. [26] demonstrated that the methanolic extract had significant activity against A. niger, the acetonic extract signifi-cantly inhibited the growth of A. alternata, and the chloroformic extract inhibited T. virens and F. solani.Ameziane et al. [93] observed a complete inhibition of the mycelial growth of G. candidum on citrus with methanolic and chloroformic bark extracts at a 10% concentration (w/v).
Bennacer et al. [40] presented that in vitro the tannic extract from walnut leaves showed a high antifungal activity against A. terreus, A. ochraceus, and A. brasilliensis with an inhibition percentage of 77% for a concentration of 40 mg/mL.Wianowska et al. [94] demonstrated that walnut green shell extracts contain a substance called juglone, which exhibits an inhibitory activity for A. alternata of 45%.Walnut extracts had little effect on the R. solani that affects the rice sheath [95].

Insecticidal Activity
More and more, plant extracts are used as an alternative to combat crop plant pests.Walnut extracts have insecticidal properties.Walnut leaves can be introduced as an effective insecticide against the rice weevil (S. oryzae).On different days, after treatment, a concentration of 0.1 g/mL of extract was the most effective (66.66%) against the rice weevil [96].Aqueous extracts of walnut leaves at a concentration of 5% caused 100% mortality in the nematode species H. bacteriophora, S. carpocapsae, S. feltiae, S. kraussei, and P. hermaphrodita [97].Walnut extracts prevented 79.94% of tomato moth (T.absoluta) oviposition at a concentration of 20% [98] and have shown greater insecticidal activity on T. griseus beetle larvae compared to the synthetic insecticide Tanalith C [99].Nevertheless, it was ineffective against the bean weevil (A.obtectus) [100].Islam and Widhalm [101] observed that juglone had toxic effects on phytophagous insects such as melon, pepper, and tomato aphids (A.gossypii); the cabbage moth (Trichoplusia ni); the corn moth (H.armigera); the red mite (T.urticae), the cabbage butterfly (P.rapae), and the vinegar midge (D. melanogaster).The WCPI (Walnut Cysteine Protease Inhibitor) that is isolated from walnuts can inhibit fungal proteases, demonstrating its biopesticide potential, being an alternative to many chemical pesticides [102].

Health Benefits and Applications of Elderberry (Sambucus nigra L.) Extracts
In Europe, elderberry fruits and flowers are used both in food and in folk medicine.The elderflowers can be used in the form of elderberry juice or elderberry syrup, and also in the form of tea, after drying.Although the flowers and berries of the elder have many health benefits, elder leaves, branches, and roots contain substances that are toxic to the body, so they should be avoided.Terzic et al. showed the potential of wine obtained from elderberries as a new food product [103].Elderberries are used in the treatment of many diseases due to their antioxidant, antitumoral, immunostimulatory, antiallergic, and antiviral benefits; their impact on obesity and metabolic disfunctions; their antidepressant potential; and their antidiabetic and antibacterial properties [12][13][14]65].
Due to the bioactive compounds, in addition to the health implications, there is a growing interest in the use of the elderberry in various fields, such as as natural additives in the food industry or as biopesticides in the growth of crop plants.
Antibacterial activity with action on the human body as well as phytosanitary activity with benefits on cultivated plants are presented.

Antibacterial Activity
Studies have indicated that the elderberry exhibits an antibacterial action that is found in the flowers, fruits, and leaves.Ferreira-Santos et al. [65] showed that aqueous extracts of the elderflowers have an antimicrobial activity against the Gram-positive bacteria S. aureus and S. epidermidis, and Ramanauskiene et al. [104] proved that ethanolic extracts had in vitro antimicrobial effects against S. aureus and B. cereus.Álvarez et al. [105] investigated the antibacterial role of peptide extracts from the elderflowers against various Gramnegative bacteria (A.salmonicida, F. psychrophilum, V. anguillarum, and V. ordalii).Antolak et al. [106] tested the effect of the elderflower extracts on six strains of A. lannensis and A. bogorensis bacteria and observed that the culture medium in the presence of elderberry is less favorable to the bacteria.Pinho et al. indicated a reduced antibacterial action on K. pneumoniae [60].Methanolic extracts of the elderflowers did not inhibit the growth of B. subtilis, P. aeruginosa, and S. aureus, whereas ethanol extracts slightly inhibited the growth of S. aureus but did not inhibit E. coli [107].The addition of 10% and 20% of elderberry extract to a culture medium inhibited Gram-positive (Streptococcus group G and group C) and Gram-negative (B.catarrhalis) bacterial growth by 70 and 99%.An infusion of elderberry leaves presented an inhibitory effect on the growth of bacteria (B.subtilis, B. megaterium, E. coli, and S. aureus) and yeasts (D. hansenii, C. shehatae, and C. tropicalis).The antimicrobial activity of extracts from the flowers was higher compared to extracts from the fruits [18].Elderflower extracts were more toxic to Gram-positive (Staphylococcus sp. and B. cereus) and Gram-negative (S. poona and P. aeruginosa) bacteria compared to fruit extracts [108].Salamon et al. showed that elderberry anthocyanins had no antimicrobial activity on S. aureus and E. faecalis [109] and that extracts from the leaves and fruits (aqueous 16%, ethanolic 5%, and methanolic 10%) had no antibacterial activity on Streptococcus sp., E. coli, P. aeruginosa, S. typhimurium, S. marcescens, P. vulgaris, E. cloacae, and K. pneumoniae [110].Elderberry extracts had less inhibition for Gram-negative (S. typhimurium, S. enteritidis, and E. coli) than Gram-positive (S. aureus) [111].Other studies indicated the antibacterial effect of elderberry extracts on Gram-positive (E.faecalis) and Gram-negative (E. coli and P. fluorescens) bacteria [112] and against M. luteus, P. mirabilis, and P. fragii bacteria [58].Elderberry extracts (0.625-15 µg/mL) also inhibited the growth of B. subtilis, S. aureus, P. aeruginosa, S. typhi, and E. coli bacteria [113].Młynarczyk et al. observed that elderflower extracts had a greater antimicrobial effect against P. aeruginosa, aqueous extracts of elder leaves had moderate activity against B. cereus and S. marces, and the fruits presented a superior potential against the bacteria that cause respiratory tract infections (a concentration of 20% of the fruit extract inhibited the growth in bacteria by 99%) [59].Kačaniová et al. [114] and Allison et al. [115] established that the extracts from elder leaves (8-10 µg/mL) had an effect against the bacteria S. enterica and S. pneumoniae, but they did not show inhibitory activity against the growth of E. coli.

Antifungal Activity
Rodino et al. demonstrated that the ethyl alcohol extract obtained from dried elderberry fruits showed the most intense inhibitory activity against the in vitro growth of P. infestans (potato mealybug) compared to the extracts from the elderflowers and fresh fruits, respectively [116].Puia et al. established that an 8% ethanol extract of elderberry was effective against Chaetomium with a percentage of 96% and Penicillium sp. with a percentage of 85.69%, but was ineffective against Fusarium sp.[117].

Insecticidal Activity
In the literature, insecticidal activity has been mainly studied on extracts from elder leaves.Jankowska and Wojciechowicz-Żytko showed that aqueous extracts from the elderberry had insecticidal effects on cabbage aphids, with a percentage of 83.34% [118].Elderberry extract produced a 20% mortality on T. castaneum (the reddish flour beetle) at a concentration of 100 mg/2 mL [119].The insecticidal effect against the horn fly (H.irritans) was observed in vitro.Jovanović et al. observed that ethanolic extracts of elder leaves against the bean weevil were ineffective [100], and Ertürk determined that the toxic effect against the third and fourth stage larvae of the moth was low (60% of the larvae did not develop) [120].
The antimicrobial action of the different parts of the walnut is demonstrated by the increased concentrations of naphthoquinones (juglone-4940 mg/100 g and 1,4naphthoquinone-3680 mg/100 g, respectively).Juglone is reported to have antimicrobial, antifungal, oxidizing, and especially anti-proliferative actions [121,122].At concentrations of 100-200 µg/mL in the growth medium, juglone irreversibly destroys the cell membranes for Listeria sp., which explains its bactericidal effect [123].1,4-Naphthoquinone exhibits antibacterial activity at concentrations of 2-10 µg/mL in the culture medium.A direct application on potato tubers in a concentration of 2 mg/mL inhibits the development of E. carotovora [124], a bacterium that produces black rot in a series of vegetables, such as carrots, red beets, onions, peppers, etc.The mechanism of the action of 1,4-naphthoquinone consists in the production of redox reactions that cause the appearance of reactive oxygen species, with a toxic effect on cell membranes [124].
From the class of flavonoids, the walnut has significant contents of apigenin, which also exhibits antimicrobial actions specific to flavonoids in general [126].
Rosmarinic, 3-p-cumaroylquinic acids, and tyrosol are included in the class of phenols and their derivatives.Numerous studies report that rosmarinic acid is a powerful antibacterial and antifungal agent, stopping the growth of pathogens such as B. cereus, S. aureus, and E. coli [129].
Similarly, bioactive compounds predominantly found only in the elderberry are quinic acid from phenols and derivatives; naringenin and rutin from flavonoids; cyanidinglucoside from anthocyanins; oleanolic acid from triterpenoids; and sambunigrin from cyanogenic glycosides.
From the class of flavonoids, naringenin and rutin stand out with significant concentrations.These compounds demonstrate actions similar to compounds common to the walnut and elderberry, which could lead to a potentiation of the antimicrobial action.
In the composition of the elderberry, there are compounds from the class of triterpenoids, such as oleanolic acid.This compound has been reported to have an antibacterial and antioxidant action on pathogens like B. cereus, S. aureus, E. coli, S. typhimurium, and C. albicans [130].
The specialized literature reports the antifungal and antibacterial action of the elderberry, mentioning sambunigrin in the composition of this plant, but a direct correlation between the presence of this compound and these activities has not yet been shown [13,58].
Gallic acid shows antifungal and antimicrobial activity [131].It possesses antifungal action on Alternaria sp.[132], Candida sp.[133], A. niger [134], and F. solani [135] and bacterial activity on Gram-positive and Gram-negative bacteria [136].Studies have indicated decreases of 33, 75, and 81% in the growth rate, depending on the concentration of gallic acid.Treatments with gallic acid can be applied to vegetables affected by diseases caused by these fungi.The action of gallic acid consists in improving the activity of chitinase and peroxidase, thus promoting plant growth [135].
Caffeic acid has antifungal, antibacterial, and antibiotic properties on some pathogens, both for plants and humans.It is used with an antifungal and antibacterial role for human pathogens such as C. albicans, S. aureus, and E. coli [137].This study also presents that gallic and caffeic acids can be used to improve the activity of some antimicrobial drugs.Concerning the applicability in agriculture, caffeic acid has an antifungal action on F. graminearum, a pathogen found in gramineae and corn.Its high pathogenicity consists not only in the decrease of productivity but also in the accumulation of some β-type mycotoxins in the plant mass [138].Practically, caffeic acid has a negative impact on fungal growth and mycotoxin production.
Like the previous compounds, p-coumaric acid is part of the class of phenols and is reported in the specialized literature to have an antifungal and antibacterial action, both on human and agricultural pathogens [139][140][141].
Ferulic acid, found in many plant sources in varying amounts, is another phenolic compound common to the walnut and elderberries.It was applied with good results in combating the proliferation of Listeria sp. and Salmonella sp., where its inhibitory effect consisted in blocking the bacterial peptidoglycan [142].It also shows antifungal activity on species such as Candida sp. and Fusarium sp.[143].
The antifungal action of vanillic acid on L. theobromae, C. gloeosporioides, F. oxysporum, P. parasiticum, P. italicum, A. niger, A. alternate, and Trichoderma sp.recorded lower effects compared to ferulic acid and p-coumaric acid [144].Regarding the antibacterial activity, vanillic acid influences both human bacterial pathogens and those from agriculture or food.
Another compound common to the walnut and elderberry that has attracted attention is quercetin, a compound from the class of flavonoids.Jaisinghani reports the antibacterial action of quercetin on S. aureus, E. coli, S. flexneri, P. vulgaris, P. aeruginosa, and L. casei var.Shirota via the broth dilution method.The quercetin inhibited the action of these bacteria in a range of 20-500 µg/mL [145].Numerous authors have reported the inhibitory effect of quercetin on Candida sp., Aspergillus sp., and Fusarium sp.[146][147][148].From the class of flavonoids, the two species have significant contents of catechin and epicatechin with antimicrobial activity specific to flavonoids in general [126].
Ursolic acid, which is part of the class of triterpenes, also has antifungal and antibacterial action [130,149].
Ellagic acid, which belongs to the class of tannins, exhibits antibacterial and antifungal activity.Extracts in ethanol and chloroform have an inhibitory effect on B. subtilis and S. aureus [150].The inhibition of pathogenic bacteria consists in the anti-enzymatic and antioxidant action [151].
Chlorogenic acid has a similar action to caffeic, rosmarinic, and ellagic acids with an antifungal and antibacterial role for human pathogens such as C. albicans, S. aureus, and E. coli [137,152].
β-Sitosterol, a compound from the phytosteroids class, in addition to other actions, possesses antifungal and antibacterial activities [153].
Considering the structure-biological activity relationship of the compounds, studying the two plants together can lead to finding a synergy between them by cumulating the bioactive effect of all the compounds, in order to find inexpensive and non-polluting alternatives for both human and plant health.

Conclusions
Taking into account the areas cultivated with walnuts and the adaptability of the elderberry (in the spontaneous flora) in the eastern part of Romania, the two crops could constitute a continuous raw material for the extraction of bioactive compounds.Most of the compounds of the two plants have antifungal and antibacterial effects on both plant and human pathogens.This aspect leads to the idea of using them as enhancers for some medicines as well as biopesticides in the context of promoting environmentally friendly technologies and products.
From the presented chemical compositions for both the walnut and the elderberry, it appears that all their components are rich in bioactive compounds.Both the elderberry and especially the walnut have been intensively studied for their individual, multiple biological activities both for human health and phytosanitary properties.
This review particularly highlights the antimicrobial activity on some pathogenic microorganisms that manifest their action on plant, leguminous, and fruit crops, which raises the hypothesis of the separate or combined use of walnut and elderberry extracts to prevent or stop the proliferation of pathogens.From this perspective, we have already initiated a research series with the aim of verifying the combined action of the phytochemicals of the two species, in order to obtain additional benefits in anticipation of a synergistic effect.

Figure 1 .
Figure 1.The main components of the walnut.

Figure 2 .
Figure 2. The component parts of elderberry.

Figure 1 .
Figure 1.The main components of the walnut.

Figure 1 .
Figure 1.The main components of the walnut.

Figure 2 .
Figure 2. The component parts of elderberry.

Figure 2 .
Figure 2. The component parts of elderberry.

Table 1 .
Main bioactive compounds of walnut kernel.

Table 2 .
Main bioactive compounds of walnut leaf.

Table 3 .
Main bioactive compounds of walnut shell.

Table 4 .
Main bioactive compounds of walnut septum.

Table 5 .
Main bioactive compounds of elderberry leaves.

Table 6 .
Main bioactive compounds of elderberry flowers.